The prognosis of tuberous sclerosis depends greatly on the number, size and location of the characteristic tumors associated with the condition. These factors affect the extent to which the tumors inhibit the normal function of body organs and the symptoms experienced as a result.
Some individuals note few symptoms and are not greatly affected by the condition, while other experience severe complications that necessitate continuing care for the duration of their life.
TSC2 Gene
Tuberous sclerosis can be caused by a mutation in the TSC1 or TSC2 gene, which causes abnormalities in the production of the proteins hamartin and tuberin respectively.
In particular, a defect in the TSC2 gene has been associated with more severe symptoms and greater probability of life threatening problems.
Morbidity
The majority of individuals with mild symptoms generally have a normal life expectancy, provided that they manage any issues that may arise from tuberous sclerosis adequately. On the other end of the spectrum, morbidity can be significant for individuals with a more severe form of the disease and may suffer from mental retardation and epilepsy.
Various symptoms may present, depending on the location of the tumors. These may include:
- Brain: Seizures, hydrocephalus, developmental disorders or mental retardation.
- Skin: Aesthetic abnormalities
- Kidneys: Decline in renal function
- Heart: Arrhythmias
- Lungs: Breathlessness
Seizures resulting from tumors in the brain are the most common symptom, which can affect babies with infantile spasms as well as adults with various types of seizures. Mental retardation is also common and is strongly linked to the presence of seizures.
Facial angiofibromas do not cause serious outcomes but are associated with significant morbidity due to the aesthetic effects that in undesired by patients.
Mortality
The most common cause of fatality for individuals with tuberous sclerosis is status epilepticus due to tumors in the brain, closely followed by bronchopneumonia and renal failure.
There is a significant risk of heart failure in fetuses and neonates with cardiac rhabdomyoma. There often develop at approximately 22-26 weeks gestation and may be responsible for causing fetal death. This occurs as a result of obstruction of the ventricles or damage to the heart muscle and contractility. However, if the infant survives the neonatal period, the lesions usually shrink or resolve completely over time and are unlikely to be fatal in adults.
Renal cysts in children or angiomyolipomas in adults also have the potential to cause renal failure and may lead to death in some cases. Particularly for larger lesions – greater than 4 cm – there is an increased risk of bleeding in the kidney. Additionally, in rare cases the renal cysts can differentiate into renal cell carcinoma and the cancer may be fatal.
For individuals with lymphangioleiomyomatosis (LAM) in the lungs, this is the most likely complication to be fatal. It is more common in females than males but is rare across the board, with less that 1% of females affected. It commonly leads to pulmonary hypertension and the final cause of death is usually pneumothorax or pulmonary failure.
It is important that all patients with tuberous sclerosis are carefully monitored by an experienced practitioner, as they can recognize signs of worsening of the condition and manage any issues appropriately. Most individuals can expect a normal lifespan in length if they receive adequate medical support.
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Further Reading